| 1. |
- Jatta, Ken, et al.
(författare)
-
Overexpression of von Hippel-Lindau protein in skeletal muscles of patients with chronic obstructive pulmonary disease
- 2009
-
Ingår i: Journal of Clinical Pathology. - London : BMJ Publishing Group Ltd. - 0021-9746 .- 1472-4146. ; 62:1, s. 70-76
-
Tidskriftsartikel (refereegranskat)abstract
- Background/aim: A Significant number of patients with chronic obstructive pulmonary disease (COPD) exhibit skeletal muscle wasting and decreased capillary area formation which have been correlated to increased mortality. The current study aimed to determine the molecular mechanisms mediating decreased capillary formation in COPD.Methods: Twenty-four COPD patients and twelve matching controls were recruited. COPD patients were divided into mild, moderate and severe groups according to GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria. Skeletal muscle biopsies were obtained from the tibialis anterior muscle. Fibre typing and capillary formation together with messenger RNA (mRNA) expression of hypoxia-inducible factors (HIF-1á and HIF-3á ), vascular endothelial growth factors (VEGF-A, -B and -C isoforms) and von Hippel Lindau (VHL) were determined. VHL expression and localization was further studied by immunohistochemistry.Results: Skeletal muscle capillary formation was significantly decreased with ascending disease severity. Compared to controls, a tendency to mRNA overexpression of HIF-1á, HIF-3á and VEGF isoforms was observed at mild and moderate COPD that decreased at the severe stage. By contrast, skeletal muscle biopsies from COPD patients exhibited significant overexpression of VHL both on the mRNA and protein levels by immunohistochemistry. VHL protein was further determined to be localized to satellite cells.Conclusions: Overexpression of VHL was identified in the skeletal muscle of patients with COPD. Increased VHL activity may exert a negative impact on transducing the hypoxic signal and may contribute to decreased capillarization in skeletal muscles of patients with COPD.
|
|
| 2. |
- Albuquerque, Joaquim F. S., et al.
(författare)
-
Adaptive changes of the enterochromaffin and gastrin cells in the rat gastrointestinal tract following subtotal colectomy
- 2006
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 41:8, s. 963-968
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. Colectomized patients often have diarrhoea and increased gastric acid secretion. Although serotonin influences gastrointestinal (GI) motility and secretion, GI serotonin-producing enterochromaffin (EC) cells have not been investigated after colectomy, nor have the antral gastrin cells. The aim of this experimental study was to investigate the GI tract in rats 8 weeks after subtotal colectomy, with particular emphasis on the frequency and distribution of EC and gastrin cells. Material and methods. Immunohistochemical techniques were used to identify the two endocrine cell types. Results. The colectomized animals had diarrhoea. Body-weight was lower and the small intestine shorter in the colectomized animals compared with sham-operated and untreated controls. In the two surgically treated groups, the antral mucosa was thinner and the small intestinal mucosa was thicker compared with that of the untreated rats, whereas the thickness of the rectum of the colectomized rats was increased compared with that of the control groups. In the colectomized animals, the number of EC cells was increased in the small intestine and rectum, whereas the numbers of both EC and gastrin cells were decreased in the antrum. Conclusions. The results indicate that colectomy exerts a significant influence on the GI mucosa and on the endocrine cell systems studied. An increased number of EC cells can result in alterations in motility and secretion, which may be important in the pathogenesis of the diarrhoea that often occurs after colectomy.
|
|
| 3. |
- Ardesjö, Brita, et al.
(författare)
-
Identification of a novel staining pattern of bile duct epithelial cells in primary sclerosing cholangitis
- 2010
-
Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1078-0998 .- 1536-4844. ; 16:2, s. 305-311
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Primary sclerosing cholangitis (PSC) is an inflammatory disease of the bile ducts with an unknown etiology. A number of autoantigens have been proposed, but an early diagnostic marker is still lacking. Our aim was to identify such an autoantigen. METHODS: Immunostaining was performed on normal human bile duct with sera from patients with PSC and controls. To identify an autoantigen a cDNA library from normal human choledochus was constructed and immunoscreened with patient sera. Using in vitro transcription and translation and immunoprecipitation we examined the immunoreactivity against PDZ domain containing 1 (PDZK1) in 35 patients with PSC, 198 control patients, and 94 healthy controls. RESULTS: We observed a previously unpublished staining pattern in which cytoplasmatic granules and apical cell membranes of biliary epithelial cells were stained by PSC sera. Strong immunoreactivity to these structures was obtained with 12 out of 35 PSC sera (34%) but not with sera from healthy controls. By screening the cDNA library we identified PDZK1 as a candidate antigen. Immunoreactivity against PDZK1 was detected in 9% of PSC patients, 2% of inflammatory bowel disease (IBD) patients, 8% of autoimmune pancreatitis patients, 18% of Grave's disease patients, and 1% of healthy controls. CONCLUSIONS: Previously unpublished, specific, and strong autoantibodies against epithelial cells of the bile duct in PSC sera were identified. Furthermore, PDZK1 is suggested as a potential new autoantigen.
|
|
| 4. |
|
|
| 5. |
- Ardesjö, Brita, et al.
(författare)
-
Immunoreactivity against Goblet cells in patients with inflammatory bowel disease.
- 2008
-
Ingår i: Inflammatory bowel diseases. - : Oxford University Press (OUP). - 1078-0998 .- 1536-4844. ; 14:5, s. 652-61
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A number of autoantibodies have been reported in inflammatory bowel disease (IBD). The aim of this study was to investigate to what extent sera from patients with IBD contain autoantibodies directed against normal human gastrointestinal mucosa. METHODS: Samples of sera from 50 patients with IBD and 50 healthy subjects were used for immunostaining of normal and affected human gastrointestinal tissues. RESULTS: Eighty-four percent of the sera from IBD patients showed immunoreactivity against goblet cells in the appendix compared with 8% of the sera from healthy subjects. Goblet cell reactivity of IBD patient sera varied between regions in the gastrointestinal tract. Sera from healthy subjects only reacted with goblet cells in the appendix. In the colon and the appendix, goblet cell reactivity of IBD sera was generally weak at the base of the crypts and gradually increased toward the lumen. Three IBD sera samples reacted with gastrin cells in the antrum. In colon biopsies from patients with ulcerative colitis, immunoreactivity against the remaining goblet cells showed an inverse correlation with inflammatory activity. CONCLUSIONS: These findings suggest that immunoreactivity against goblet cells may be of central importance in the pathogenesis of IBD. Identification of goblet cell antigens could lead to a better understanding of IBD and provide a new diagnostic tool.
|
|
| 6. |
|
|
| 7. |
- Portela-Gomes, Guida M., et al.
(författare)
-
Co-localization of chromogranins and neuroendocrine hormones in the human gastrointestinal mucosa
- 1996
-
Ingår i: Regulatory Peptides. - : Elsevier BV. - 0167-0115 .- 1873-1686. ; 64:1, s. 154-154
-
Recension (refereegranskat)abstract
- Co-localization of chromogranin (Cg) A, B and C has been studied in different neuroendocrine cell types in histologically normal mucosa from human gastrointestinal (GI) tract (corpus, antrum, duodenum, ileum and colon). Single, double and triple immunofluorescence stains were used, including appropriate controls. The results showed that whereas CgA cells predominated in all GI-regions, CgB cells were numerous in antrum, few in duodenum (only villi), and almost non-existent in corpus, ileum and colon. CgC cells were sparse in antrum and duodenum (only crypts). Concerning co-localization, gastrin cells harboured CgA and B, some also CgC. All EC cells displayed CgA-immunoreactivity. The EC cells localized in the luminal 23 of the antral mucosa and those in the duodenal villi also contained CgB. Occasionally the EC cells in the duodenal crypts displayed CgC. Almost all cells showing immunoreaction to enteroglucagon/PYY, secretin, neurotensin, or GIP were positive for CgA. Somatostatin cells were with few exceptions CgA-negative, and displayed neither CgB nor C immunoreactivity. CCK cells, indirectly identified, were negative for CgB and C, probably also for CgA.Regarding intracellular localization, CgA and C were seen closer to the basal cell regions, whereas CgB was found more diffusely spread throughout the cytoplasm. This difference in localization between chromogranins suggests that not all secretory granules contain CgA or that CgB may appear in a non-granular form. The results confirm previous findings that CgA occurs in most neuroendocrine cell types of the GI-tract. In most gastrin cells there were two sets of chromogranins, CgA and B, a minority all three chromogranins. All EC cells were CgA immunoreactive, a minority also contained CgB (antrum + duodenal villi) or CgC (duodenal crypts), but not both. All CCK cells seem to be devoid of chromogranins. With few exceptions the same was true of the somatostatin cells. An interesting question posed by the present study is why the chromogranins occur in varying extent and composition in the different cell types.
|
|
| 8. |
|
|
| 9. |
- Portela-Gomes, Guida M., et al.
(författare)
-
Granins and granin-related peptides in neuroendocrine tumours
- 2010
-
Ingår i: Regulatory Peptides. - : Elsevier BV. - 0167-0115 .- 1873-1686. ; 165:1, s. 12-20
-
Forskningsöversikt (refereegranskat)abstract
- This review focus on neuroendocrine tumours (NETs), with special reference to the immunohistochemical analysis of granins and granin-related peptides and their usefulness in identifying and characterizing the great diversity of NET types. Granins, their derived peptides, and complex protein-processing enzyme systems that cleave granins and prohormones, have to some extent cell-specific expression patterns in normal and neoplastic NE cells. The marker most commonly used in routine histopathology to differentiate between non-NETs and NETs is chromogranin (Cg) A, to some extent CgB. Other members of the granin family may also be of diagnostic value by identifying special NET types, e.g. secretogranin (Sg) VI was only found in pancreatic NETs and phaeochromocytomas. SgIII has recently arisen as an important NET marker; it was strongly expressed in NETs, with some exceptions - phaeochromocytomas expressed few cells and parathyroid adenomas none. Some expression patterns of granin-related peptides seem valuable in differentiating between some benign and malignant NETs, some may also provide prognostic information, among which: well-differentiated NET types expressed more CgA epitopes than the poorly differentiated ones, except insulinomas, where the opposite was noted; medullary thyroid carcinomas containing few cells immunoreactive to a CgB antibody were related to a bad prognosis; C-terminal secretoneurin visualized a cell type related to malignancy in phaeochromocytomas. Further research will probably establish new staining patterns with marker functions for granins in NETs which may be of histopathological diagnostic value.
|
|
| 10. |
- Portela-Gomes, Guida M., et al.
(författare)
-
Immunohistochemical and Biochemical Studies with Region-Specific Antibodies to Chromogranins A and B and Secretogranins II and III in Neuroendocrine Tumors
- 2010
-
Ingår i: Cellular and Molecular Neurobiology. - New York, USA : SPRINGER/PLENUM PUBLISHERS. - 1573-6830. ; , s. 1147-1153
-
Konferensbidrag (refereegranskat)abstract
- This short review deals with our investigations in neuroendocrine tumors (NETs) with antibodies against defined epitopes of chromogranins (Cgs) A and B and secretogranins (Sgs) II and III. The immunohistochemical expression of different epitopes of the granin family of proteins varies in NE cells in normal human endocrine and non-endocrine organs and in NETs, suggesting post-translational processing. In most NETs one or more epitopes of the granins were lacking, but variations in the expression pattern occurred both in benign and malignant NETs. A few epitopes displayed patterns that may be valuable in differentiating between benign and malignant NET types, e.g., well-differentiated NET types expressed more CgA epitopes than the poorly differentiated ones and C-terminal secretoneurin visualized a cell type related to malignancy in pheochromocytomas. Plasma concentrations of different epitopes of CgA and CgB varied. In patients suffering from carcinoid tumors or endocrine pancreatic tumors the highest concentrations were found with epitopes from the mid-portion of CgA. For CgB the highest plasma concentrations were recorded for the epitope 439-451. Measurements of SgII showed that patients with endocrine pancreatic tumors had higher concentrations than patients with carcinoid tumors or pheochromocytomas. SgIII was not detectable in patients with NETs.
|
|
